Abstract

The intestine is an organ where immune, metabolic and neuroendocrine regulation is coordinated with the rapid renewal of the tissue via progenitor somatic stem cells (PSSCs). However, how these cells are influenced by each of the different physiological activities of the intestine is still unclear. We report here that in Drosophila, systemic infection significantly increased PSSC numbers, which was mimicked by expressing a constitutive form of the immune receptor Toll in PSSCs and blocked when Toll was silenced via RNAi. Toll was important for the transition of Intestinal Stem Cells (ISCs) to Enteroblasts (EBs) and Toll silencing in either in the absence of infection resulted in the long-term reduction of PSSC numbers. This phenotype was also observed in mutants of the Peptidoglycan Recognition Protein-SA (PGRP-SA), acting upstream of Toll. PGRP-SA mutations or Toll-RNAi in progenitor cells led to a marked decrease in gut microbiota, implying that a regularly renewed intestine was crucial for maintenance of normal numbers of commensal bacteria. Infection or constitutive Toll signalling in progenitor cells triggered FOXO-dependent transcription in enterocytes. Our results show that PGRP-SA-Toll immunity is crucial for gut homeostasis.